1. Technical Field
This invention concerns the field of spectroscopy and, more specifically, the use of spectrophotometry to determine gas phase concentrations.
2. Background Art
There are many methods used to detect and/or determine the concentration of an analyte in a mixture or solution. See, for example, U.S. Pat. Nos. 4,314,344, 4,427,772, 4,525,265, 4,795,707, 4,843,867, 5,139,957, 5,167,927, 5,474,908, 5,482,684, 5,516,489, 5,518,591, 5,600,142, 5,608,156, 5,788,925, 5,789,175, 5,847,392, 5,847,393, 5,872,359, 5,892,229, 5,938,917, 5,942,754, 5,972,199, 6,075,246, 6,156,267, and 6,189,368; and European Patent Application No. EP 1,016,421. (All of the foregoing documents, as well as all other documents cited or otherwise referenced herein, are incorporated herein in their entireties for all purposes.)
Some of those documents concern detecting and/or determining the concentration of a species in gas, vapor, or plasma. See, e.g., U.S. Pat. Nos. 4,314,344, 4,843,867, 5,139,957, 5,167,927, 5,482,684, 5,516,489, 5,600,142, 5,608,156, 5,788,925, 5,789,175, 5,847,392, 5,847,393, 5,872,359, 5,892,229, 6,075,246, 6,156,267, 6,189,368; and European Patent Application No. EP 1,016,421.
Some of those documents concern detecting and/or determining the concentration of hydrogen peroxide. See, e.g., U.S. Pat. Nos. 4,427,772, 4,525,265, 4,795,707, 4,843,867, 5,139,957, 5,167,927, 5,474,908, 5,516,489, 5,518,591, 5,600,142, 5,608,156, 5,788,925, 5,789,175, 5,847,392, 5,847,393, 5,872,359, 5,892,229, 5,938,917, 5,942,754, 5,972,199, 6,156,267, 6,189,368; and European Patent Application No. EP 1,016,421.
Some of those documents concern detecting and/or determining the concentration of hydrogen peroxide using spectrophotometry, e.g., using infrared or near-infrared energy. See, e.g., U.S. Pat. Nos. 5,600,142, 5,847,392, 5,847,393, 5,872,359, 5,892,229, 5,942,754; and European Patent Application No. EP 1,016,421.
It is known to determine successive values of a parameter for analytes that decompose after the decomposition has begun and to extrapolate from those successive values back to time zero (the moment just before decomposition begins) to estimate the value of the parameter at time zero. To applicants"" knowledge, such a method has not been used for peracids or peroxides (e.g., hydrogen peroxide).
Hydrogen peroxide is used in connection with bleaching, sterilization, and other processes, and there is a need to be able to measure or determine its concentration accurately. In particular, for vapor phase sterilization, the concentration of hydrogen peroxide in the gas phase must be accurately known; however, development of a method for accurately determining the concentration of hydrogen peroxide in the gas phase is hampered by the fact that hydrogen peroxide decomposes in the gas phase. Hydrogen peroxide decomposition increases with increasing temperature (at room temperature, an increase of 10xc2x0 C. is believed to more than double the rate of decomposition), with increasing pH (especially in the alkaline range), with increasing contamination (e.g., with transition metals), and with exposure to light (particularly ultraviolet light).
Hydrogen peroxide is typically sold in aqueous solution, for example, at concentrations of 3% w/w, 10% w/w, 30% w/w, 35% w/w, and higher (e.g., 70% w/w), and the manufacturers generally add proprietary stabilizers (e.g., chelants/sequestrants such as organic and inorganic phosphates and/or stannates and/or silicates) to the liquid solution to minimize decomposition. Unfortunately, these stabilizers do not function in the vapor phase and once an aqueous liquid solution of hydrogen peroxide is vaporized, as it typically is in hydrogen peroxide vapor phase sterilization processes, decomposition of the hydrogen peroxide immediately begins and continues unabated.
Continuous decomposition of hydrogen peroxide in the vapor phase makes it all the more difficult to determine a relationship between the concentration of the hydrogen peroxide in the vapor phase and a physical property of the hydrogen peroxide that can be measured rapidly (e.g., absorbance of spectral energy within a preselected spectral region characteristic of the hydrogen peroxide) and which relationship can therefore be used to monitor the hydrogen peroxide concentration (e.g., during a hydrogen peroxide sterilization process). This is because such a relationship must be established experimentally and doing so requires, among other things, collecting a sufficient number of replicate data points in real time, but that unfortunately is while the hydrogen peroxide itself is continuing to decompose. In other words, while the physical property indicative of the concentration of hydrogen peroxide is being measured repeatedly so that the relationship between concentration and the physical property can be established, the hydrogen peroxide concentration is decreasing and the measured value of the physical property is changing.
Despite all the attempts that have been made, the need still remains for a rapid and accurate method for determining hydrogen peroxide concentration in the vapor phase. More generally, the need still exists for a rapid and accurate method for determining the concentration of an analyte that decomposes.
A rapid and accurate method for determining hydrogen peroxide concentration in the vapor phase has now been developed. More generally, a rapid and accurate method for determining the concentration of an analyte that decomposes and/or whose spectral data are xe2x80x9cpressure sensitivexe2x80x9d (as defined herein) has now been developed. As explained below, applicants discovered that hydrogen peroxide not only decomposes but that its spectral data are pressure sensitive.
Thus, for hydrogen peroxide, the method of determining the concentration makes use of a monotonic functional relationship between the concentration of hydrogen peroxide in the vapor phase and the total (integrated) absorbance of spectral energy within a preselected spectral region characteristic of hydrogen peroxide, preferably the spectral region of wavenumbers 1180 cmxe2x88x921 (approximately 8475 nanometers) through 1331 cmxe2x88x921 (approximately 7513 nanometers). Thus, a first part of the invention concerns a method for using the relationship to determine (or estimate or predict) from the integrated absorbance of spectral energy for an unknown (i.e., unknown sample) what the concentration of hydrogen peroxide (or other analyte) is in that unknown. A second part of the invention concerns a method for establishing or determining the monotonic functional relationship for hydrogen peroxide (or other analyte).
In connection with the development of the second part of the invention as it applies to hydrogen peroxide, applicants made the surprising discovery that at pressures below about 230 torr (approximately 30.7 kPa), the integrated absorbance for hydrogen peroxide is about 20% lower than it would otherwise be if the pressure were above the pressure at which this phenomenon occurs or at least becomes noticeable (i.e., above about 230 torr). The significance of this is that use of data subject to this phenomenon (i.e., integrated absorbance data that are significantly lower than they would otherwise be) to establish the monotonic functional relationship will result in erroneous predicted hydrogen peroxide concentrations in some cases. Applicants do not know why this phenomenon of significantly lower integrated absorbance occurs.
As indicated herein, if it is desired to estimate, the vapor phase hydrogen peroxide concentration in an unknown, the integrated absorbance for the unknown over the spectral region of interest is determined and the previously established monotonic functional relationship between concentration and integrated absorbance is used. That relationship is typically established from absorbance data for different known hydrogen peroxide concentrations. Applicants discovered that, most surprisingly, for a constant amount of hydrogen peroxide in a chamber (and therefore for which the integrated absorbance within the spectral region of interest was expected to remain constant), when increasing amounts of dry air (which is essentially inert to the hydrogen peroxide) were added to the chamber, thereby raising the total pressure, the integrated absorbance in fact varied: it was approximately constant at total pressures from about 230 torr up to atmospheric pressure but was approximately 20% lower at total pressures below that point.
Accordingly, if the relationship between hydrogen peroxide concentration and integrated absorbance must be known for a constant pressure (e.g., atmospheric pressure) because, for example, the relationship will be used to predict hydrogen peroxide concentration in a system operating at that pressure (e.g., atmospheric pressure), the data used to establish the relationship cannot be generated at a pressure that is too low. If too low a pressure is used for obtaining some or all of the data from which the relationship between integrated absorbance and concentration will be established, the relationship determined from that data will not accurately reflect the relationship at the higher system operating pressure throughout at least some or all of the concentration range. As a result, an integrated absorbance measured at the higher system operating pressure that falls within the xe2x80x9cerroneousxe2x80x9d part of the monotonic functional relationship determined using the xe2x80x9clowxe2x80x9d integrated absorbance values will predict too high a concentration (i.e., will indicate a concentration in the system higher than is actually present). Such over-prediction of the concentration cannot be tolerated in any application in which the hydrogen peroxide concentration must be accurately known (e.g., hydrogen peroxide sterilization systems).
As will be explained in more detail below, applicants solved this problem in the following manner. While obtaining the data for establishing the hydrogen peroxide concentration-absorbance relationship, they intentionally rapidly added to the hydrogen peroxide aliquots of known concentration a sufficient amount of a gas essentially inert (i.e., chemically, spectrally, etc.) to the hydrogen peroxide (namely, dry air) to bring the total pressure above the pressure P at which the xe2x80x9clowxe2x80x9d integrated absorbance values would otherwise have been obtained so that the data were all obtained at pressures above pressure P.
Thus, in a first aspect, the invention concerns a method for determining the monotonic functional relationship between (A) the integrated absorbance of spectral energy within a spectral region of interest of an analyte that decomposes during the time experimental spectral data for determining the relationship are being obtained and whose spectral data are pressure sensitive below a total pressure P and (B) the concentration of the analyte before decomposition commences, knowledge of the monotonic functional relationship being useful for determining the concentration of the analyte in an unknown that is at a total pressure not less than pressure P from the integrated absorbance of spectral energy within the spectral region of interest for the unknown, the method comprising the steps:
(a) for a first known initial concentration of the analyte and while intentionally maintaining the total pressure at a pressure not less than pressure P because of the spectral data being pressure sensitive below pressure P: (i) determining the integrated absorbance of spectral energy within the spectral region of interest at a first time after the commencement of the obtention of spectral data, (ii) determining the integrated absorbance of spectral energy within the spectral region of interest at one or more times subsequent to the first time and different from each other if more than one subsequent time is used, and (iii) extrapolating from the integrated absorbance for the first time and the one or more subsequent times to the time at which the decomposition of the analyte commences to thereby establish at a time before the decomposition commences an estimated integrated absorbance of spectral energy within the spectral region of interest for the first known initial concentration;
(b) for each of one or more additional known initial concentrations of the analyte different from the first known concentration and different from each other if more than one additional initial concentration is used and while intentionally maintaining the total pressure at a pressure not less than pressure P because of the spectral data being pressure sensitive below pressure P: (i) determining the integrated absorbance of spectral energy within the spectral region of interest at a first time after the commencement of the obtention of spectral data, (ii) determining the integrated absorbance of spectral energy within the spectral region of interest at one or more times subsequent to the first time and different from each other if more than one subsequent time is used, and (iii) extrapolating from the integrated absorbance for the first time and the one or more subsequent times to the time at which the decomposition of the analyte commences to thereby establish at a time before the decomposition commences an estimated integrated absorbance of spectral energy within the spectral region of interest for each of the one or more additional known initial concentrations; and
(c) associating each of the known initial concentrations with its respective estimated integrated absorbance of spectral energy within the spectral region of interest to thereby determine for the analyte at a total pressure not less than pressure P the monotonic functional relationship between the concentration before the decomposition commences and the integrated absorbance of spectral energy within the spectral region of interest of the analyte.
In a second aspect, the invention concerns a method for determining in an unknown the concentration of an analyte that decomposes and whose spectral data are pressure sensitive below a total pressure P, the method comprising the steps: (d) while intentionally maintaining the total pressure at a pressure not less than pressure P because of the spectral data being pressure sensitive below pressure P, carrying out the method of the first aspect of this invention to determine the monotonic functional relationship for the analyte, (e) while intentionally maintaining the total pressure at a pressure not less than pressure P because of the spectral data being pressure sensitive below pressure P, determining the integrated absorbance for the unknown within the spectral region of interest, and (f) from the monotonic functional relationship determined in step (d) and the integrated absorbance determined in step (e), determining the concentration of the analyte in the unknown.
In a third aspect, the invention concerns a method for determining in an unknown the concentration of an analyte that decomposes and whose spectral data are pressure sensitive below a total pressure P, a monotonic functional relationship between the concentration of the analyte and integrated absorbance at a total pressure not less than pressure P having been previously established using the method of the first aspect of this invention, the method comprising the steps: (a) while intentionally: maintaining the total pressure at a pressure not less than pressure P because of the spectral data being pressure sensitive below pressure P, determining the integrated absorbance for the unknown within the spectral region of interest and (b) from the monotonic functional relationship previously determined at a total pressure not less than pressure P using the method of the first aspect of this invention and the integrated absorbance determined in step (a), determining the concentration of the analyte in the unknown.
In a fourth aspect, the invention concerns a method for determining the monotonic functional relationship between (A) the integrated absorbance of spectral energy within a spectral region of interest of an analyte that is a peracid or a peroxide and that decomposes during the time experimental spectral data for determining the relationship are being obtained and (B) the concentration of the analyte before decomposition commences, knowledge of the monotonic functional relationship being useful for determining the concentration of the analyte in an unknown from the integrated absorbance of spectral energy within the spectral region of interest for the unknown, the method comprising the steps:
(a) for a first known initial concentration of the analyte: (i) determining the integrated absorbance of spectral energy within the spectral region of interest at a first time after the commencement of the obtention of spectral data, (ii) determining the integrated absorbance of spectral energy within the spectral region of interest at one or more times subsequent to the first time and different from each other if more than one subsequent time is used, and (iii) extrapolating from the integrated absorbance for the first time and the one or more subsequent times to the time at which the decomposition of the analyte commences to thereby establish at a time before the decomposition commences an estimated integrated absorbance of spectral energy within the spectral region of interest for the first known initial concentration;
(b) for each of one or more additional known initial concentrations of the analyte different from the first known concentration and different from each other if more than one additional initial concentration is used: (i) determining the integrated absorbance of spectral energy within the spectral region of interest at a first time after the commencement of the obtention of spectral data, (ii) determining the integrated absorbance of spectral energy within the spectral region of interest at one or more times subsequent to the first time and different from each other if more than one subsequent time is used, and (iii) extrapolating from the integrated absorbance for the first time and the one or more subsequent times to the time at which the decomposition of the analyte commences to thereby establish at a time before the decomposition commences an estimated integrated absorbance of spectral energy within the spectral region of interest for each of the one or more additional known initial concentrations; and
(c) associating each of the known initial concentrations with its respective estimated integrated absorbance of spectral energy within the spectral region of interest to thereby determine for the analyte the monotonic functional relationship between the concentration before the decomposition commences and the integrated absorbance of spectral energy within the spectral region of interest of the analyte.
In a fifth aspect, the invention concerns a method for determining in an unknown the concentration of an analyte that is a peracid or a peroxide and that decomposes, the method comprising the steps: (d) carrying out the method of the fourth aspect of the invention to determine the monotonic functional relationship for the analyte, (e) determining the integrated absorbance for the unknown within the spectral region of interest, and (f) from the monotonic functional relationship determined in step (d) and the integrated absorbance determined in step (e), determining the concentration of the analyte in the unknown.
In a sixth aspect, the invention concerns a method for determining in an unknown the concentration of an analyte that is a peracid or a peroxide and that decomposes, a monotonic functional relationship between the concentration of the analyte and integrated absorbance having been previously established using the method of the fourth aspect of the invention, the method comprising the steps: (a) determining the integrated absorbance for the unknown within the spectral region of interest and (b) from the monotonic functional relationship previously determined using the method of the fourth aspect of the invention and the integrated absorbance determined in step (a), determining the concentration of the analyte in the unknown.
In a seventh aspect, the invention concerns a method for determining the monotonic functional relationship between (A) the integrated absorbance of spectral energy within a spectral region of interest of an analyte in the gas phase whose spectral data are pressure sensitive below total pressure P and (B) the concentration of the analyte, knowledge of the monotonic functional relationship being useful for determining the concentration of the analyte in a gas phase unknown that is at a total pressure not less than pressure P from the integrated absorbance of spectral energy within the spectral region of interest for the unknown, the method comprising the steps:
(a) for a first known initial concentration of the analyte and while intentionally maintaining the total pressure at a pressure not less than pressure P because of the spectral data being pressure sensitive below pressure P, determining the integrated absorbance of spectral energy within the spectral region of interest for the first known initial concentration;
(b) for each of one or more additional known initial concentrations of the analyte different from the first known concentration and different from each other if more than one additional initial concentration is used and while intentionally maintaining the total pressure at a pressure not less than pressure P because of the spectral data being pressure sensitive below pressure P, determining the integrated absorbance of spectral energy within the spectral region of interest for each of the one or more additional known initial concentrations; and
(c) associating each of the known initial concentrations with its respective integrated absorbance of spectral energy within the spectral region of interest to thereby determine for the analyte at a total pressure not less than pressure P the monotonic functional relationship between the concentration and the integrated absorbance of spectral energy within the spectral region of interest of the analyte.
In an eighth aspect, the invention concerns a method for determining in a gas phase unknown the concentration of an analyte whose spectral data are pressure sensitive below a total pressure P, the method comprising the steps: (d) while intentionally maintaining the total pressure at a pressure not less than pressure P because of the spectral data being pressure sensitive below pressure P, carrying out the method of the seventh aspect of the invention to determine the monotonic functional relationship for the analyte, (e) while intentionally maintaining the total pressure at a pressure not less than pressure P because of the spectral data being pressure sensitive below pressure P, determining the integrated absorbance for the unknown within the spectral region of interest, and (f) from the monotonic functional relationship determined in step (d) and the integrated absorbance determined in step (e), determining the concentration of the analyte in the unknown.
In a ninth aspect, the invention concerns a method for determining in an unknown the concentration of an analyte whose spectral-data are pressure sensitive below a total pressure P, a monotonic functional relationship between the concentration of the analyte and integrated absorbance having been previously established using the method of the seventh aspect of the invention, the method comprising the steps: (a) while intentionally maintaining the total pressure at a pressure not less than pressure P because of the spectral data being pressure sensitive below pressure P, determining the integrated absorbance for the unknown within the spectral region of interest and (b) from the monotonic functional relationship previously determined using the method of the seventh aspect of the invention and the integrated absorbance determined in step (a), determining the concentration of the analyte in the unknown.
In preferred embodiments of the methods of the invention: pressure P is determined prior to carrying out the other steps of one or more of the methods; and/or the total pressure is maintained in each of the steps of one or more of the methods at not less than pressure P by adding to the analyte as needed to raise the pressure a gas that is inert to the analyte; and/or the gas that is inert to the analyte is dry air; and/or the analyte is a sterilant; and/or the analyte is a volatile inorganic or organic peroxidant; and/or the analyte is a peracid or a peroxide; and/or the analyte is a peracid; and/or the analyte is a peroxide; and/or the analyte is hydrogen peroxide; and/or the spectral region of interest is the infrared region; and/or the spectral region of interest is from about 1180 cmxe2x88x921 to about 1331 cmxe2x88x921.
This invention provides a rapid and accurate method for determining hydrogen peroxide concentration, as well the concentration of other analytes and particularly in the vapor phase. This invention has still other features and benefits that will be apparent to one skilled in the art.